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Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions
Amrie C. Grammer, Rebecca Slota, Randy Fischer, Hanan Gur, Hermann Girschick, Cheryl Yarboro, Gabor G. Illei, and Peter E. Lipsky
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Published March 1, 2007 - More info
J Clin Invest. 2007;117(3):835–835. https://doi.org/10.1172/JCI19301C1.
© 2007 The American Society for Clinical Investigation
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Abstract
To determine the role of CD154-CD40 interactions in the B cell overactivity exhibited by patients with active systemic lupus erythematosus (SLE), CD19+ peripheral B cells were examined before and after treatment with humanized anti-CD154 mAb (BG9588, 5c8). Before treatment, SLE patients manifested activated B cells that expressed CD154, CD69, CD38, CD5, and CD27. Cells expressing CD38, CD5, or CD27 disappeared from the periphery during treatment with anti-CD154 mAb, and cells expressing CD69 and CD154 disappeared from the periphery during the post-treatment period. Before treatment, active-SLE patients had circulating CD38bright Ig-secreting cells that were not found in normal individuals. Disappearance of this plasma cell subset during treatment was associated with decreases in anti–double-stranded DNA (anti-dsDNA) Ab levels, proteinuria, and SLE disease activity index. Consistent with this finding, peripheral B cells cultured in vitro spontaneously proliferated and secreted Ig in a manner that was inhibited by anti-CD154 mAb. Finally, the CD38+/++IgD+, CD38+++, and CD38+IgD– B cell subsets present in the peripheral blood also disappeared following treatment with humanized anti-CD154. Together, these results indicate that patients with active lupus nephritis exhibit abnormalities in the peripheral B cell compartment that are consistent with intensive germinal center activity, are driven via CD154-CD40 interactions, and may reflect or contribute to the propensity of these patients to produce autoantibodies.
Authors
Amrie C. Grammer, Rebecca Slota, Randy Fischer, Hanan Gur, Hermann Girschick, Cheryl Yarboro, Gabor G. Illei, Peter E. Lipsky
Original citation: J. Clin. Invest.112:1506-1520 (2003). doi:10.1172/JCI200319301.
Citation for this corrigendum: J. Clin. Invest.117:835 (2007). doi:10.1172/JCI19301C1.
During the preparation of the manuscript, errors were introduced into Figure 3 that affected paragraph 6 in Results. The corrected paragraph and figure appear below.
The authors regret this error.
Expression of differentiation and activation antigens during and after treatment of active-SLE patients with humanized anti-CD154 mAb (BG9588, 5c8). CD38positive B cells in the circulation of the active-SLE patients disappeared from the peripheral blood during the treatment regimen with humanized anti-CD154 mAb (Figures 2b, 2c, and 3a). Specifically, before the treatment regimen, 63.8% ± 4.1% of the B cells were CD38positive. At 4–8 weeks after initiation of treatment, the percentage of CD38positive B cells in the circulation had dropped to 22.7% ± 15.0% (P = 0.024 compared with before treatment). Withdrawal of treatment led to a reappearance of CD38positive B cells in the circulation (79.3% ± 8.6%) at the earliest time point tested, 2 months after treatment, at a percentage that was not different from the pretreatment percentage (P > 0.05). Of note, this trend was significant for both the pre-switch IgD+ (P = 0.018) and the post-switch IgD– (P = 0.022) B cell subsets.
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